哮喘及上皮的气道重塑:在一个新时代的边缘
2024/04/24
摘要
哮喘是一种慢性、异质性的气道疾病，通常以结构性改变统称为气道重塑为特征。在环境刺激（包括病原体、过敏原和污染物）的作用下，上皮可以通过涉及多种介质的炎症级联反应来启动重塑，这些介质对结构和免疫细胞都具有下游效应。这些介质包括上皮细胞因子胸腺样胸腺上皮淋巴生成素（TSLP）、白细胞介素33和白细胞介素25，它们通过上皮细胞与成纤维细胞之间、肥大细胞与气道平滑肌细胞之间以及与免疫细胞（如巨噬细胞）之间的相互作用促进气道重塑。上皮还可以在支气管收缩期间的机械应力作用下独立于炎症启动气道重塑。此外，据信上皮成分的遗传和表观遗传变化会影响重塑。益于基因测序和成像技术的发展，我们在本文中回顾了对上皮和上皮细胞因子在驱动气道重塑中作用的最新认识。我们还探讨了如何通过针对上皮和上皮细胞因子的新型和现有治疗方法来改善气道重塑。
Airway remodelling in asthma and the epithelium: on the edge of a new era
Gilda Varricchi, Christopher E Brightling, Christopher Grainge, Bart N Lambrecht, Pascal Chanez
Abstract
Asthma is a chronic, heterogeneous disease of the airways, often characterised by structural changes known collectively as airway remodelling. In response to environmental insults, including pathogens, allergens and pollutants, the epithelium can initiate remodelling via an inflammatory cascade involving a variety of mediators that have downstream effects on both structural and immune cells. These mediators include the epithelial cytokines thymic stromal lymphopoietin (TSLP), interleukin 33 and interleukin 25, which facilitate airway remodelling through cross-talk between epithelial cells and fibroblasts, and between mast cells and airway smooth muscle cells, as well as through signalling with immune cells like macrophages. The epithelium can also initiate airway remodelling independently of inflammation in response to the mechanical stress present during bronchoconstriction. Furthermore, genetic and epigenetic alterations to epithelial components are believed to influence remodelling. Here, we review recent advances in our understanding of the roles of the epithelium and epithelial cytokines in driving airway remodelling, facilitated by developments in genetic sequencing and imaging techniques. We also explore how new and existing therapeutics that target the epithelium and epithelial cytokines could modify airway remodelling.
哮喘是一种慢性、异质性的气道疾病，通常以结构性改变统称为气道重塑为特征。在环境刺激（包括病原体、过敏原和污染物）的作用下，上皮可以通过涉及多种介质的炎症级联反应来启动重塑，这些介质对结构和免疫细胞都具有下游效应。这些介质包括上皮细胞因子胸腺样胸腺上皮淋巴生成素（TSLP）、白细胞介素33和白细胞介素25，它们通过上皮细胞与成纤维细胞之间、肥大细胞与气道平滑肌细胞之间以及与免疫细胞（如巨噬细胞）之间的相互作用促进气道重塑。上皮还可以在支气管收缩期间的机械应力作用下独立于炎症启动气道重塑。此外，据信上皮成分的遗传和表观遗传变化会影响重塑。益于基因测序和成像技术的发展，我们在本文中回顾了对上皮和上皮细胞因子在驱动气道重塑中作用的最新认识。我们还探讨了如何通过针对上皮和上皮细胞因子的新型和现有治疗方法来改善气道重塑。
(中日友好医院呼吸与危重症医学科 顾宪民 摘译 林江涛 审校)
(Eur Respir J. 2024 Apr 12:2301619. doi: 10.1183/13993003.01619-2023.)
(Eur Respir J. 2024 Apr 12:2301619. doi: 10.1183/13993003.01619-2023.)
Airway remodelling in asthma and the epithelium: on the edge of a new era
Gilda Varricchi, Christopher E Brightling, Christopher Grainge, Bart N Lambrecht, Pascal Chanez
Abstract
Asthma is a chronic, heterogeneous disease of the airways, often characterised by structural changes known collectively as airway remodelling. In response to environmental insults, including pathogens, allergens and pollutants, the epithelium can initiate remodelling via an inflammatory cascade involving a variety of mediators that have downstream effects on both structural and immune cells. These mediators include the epithelial cytokines thymic stromal lymphopoietin (TSLP), interleukin 33 and interleukin 25, which facilitate airway remodelling through cross-talk between epithelial cells and fibroblasts, and between mast cells and airway smooth muscle cells, as well as through signalling with immune cells like macrophages. The epithelium can also initiate airway remodelling independently of inflammation in response to the mechanical stress present during bronchoconstriction. Furthermore, genetic and epigenetic alterations to epithelial components are believed to influence remodelling. Here, we review recent advances in our understanding of the roles of the epithelium and epithelial cytokines in driving airway remodelling, facilitated by developments in genetic sequencing and imaging techniques. We also explore how new and existing therapeutics that target the epithelium and epithelial cytokines could modify airway remodelling.
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KLF5介导的气道上皮细胞凋亡通过 miR-182-5p/TLR4轴导致哮喘小鼠的气道炎症
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